An Italian Survey and Focus Groups on Fibromyalgia Impairment: Impact on Work and Possible Reasonable Accommodations.

Fibromyalgia symptoms affect the sufferers' working life; however, through reasonable accommodations in workplaces, they can continue to work satisfactorily. There are no Italian studies on factors that facilitate or hinder fibromyalgia-affected people's working life. Our objective was to explore, in a pre-pandemic setting, the quality of working life of fibromyalgia sufferers and reasonable accommodations to improve it. Quantitative and qualitative methods were applied; a survey-questionnaire, participatory-developed, was online-administered to a sample of self-reported FM sufferers (N = 1176). Then, two Focus Groups (FGs), involving 15 fibromyalgia-affected women, were held. Data were analyzed by a thematic analysis approach. Among survey-respondents, 20% were unemployed and only 14% went to work gladly. Variability of pain (84%) and fatigue (90%) were the most perceived reasons for difficulties at work. Negative relationships at work were reported by most participants. The FGs' discussions addressed different strategies for overcoming the main obstacle of "not being believed by colleagues and employers" and reasonable accommodations. However, a negative hopeless attitude towards the solution of problems at work was also apparent. Different critical issues in the workplace emerged from the survey and the FGs. Coordinated actions, according to a transdisciplinary approach, are needed to manage fibromyalgia-induced difficulties in the workplace.

An Observational Study on Chronic Pain Biomarkers in Fibromyalgia and Osteoarthritis Patients: Which Role for Mu Opioid Receptor's Expression on NK Cells?

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells' functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the "Mu opioid receptor reserve theory".

An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity.

Background and Objectives: Non-cancer chronic pain (CP) results from the interaction between genetic and environmental factors. Twin studies help to estimate genetic and environmental contributions to complex traits such as CP. To date, twin studies on the heritability of pain phenotypes have relied almost exclusively on specific diagnoses, neglecting pain intensity. This study aims to estimate the genetic and environmental contributions to CP occurrence as a wide phenotype and its intensity among a non-clinical population. Materials and Methods: A nationwide online survey was conducted in February 2020 on 6000 adult twins enrolled in the Italian Twin Registry. A five-item questionnaire, designed and validated by our study group, was administered to detect the CP condition along with its intensity, underlying causes or triggers, treatments, and self-perceived efficacy. The twin study design was used to infer the relative weight of genes and environment on CP occurrence and intensity, and biometrical modelling was applied to these phenotypes. Results: A total of 3258 twins, aged ≥18, replied to the online survey (response rate 54%). These included 762 intact pairs (mean age: 39 years; age range: 18-82 years; 34% male; CP prevalence: 24%), of whom 750 pairs were subjected to biometrical modelling after the exclusion of pairs with either unknown zygosity or cancer-associated CP. Broad-sense heritability estimates were driven by non-additive genetic effects and were 0.36 (0.19-0.51) for CP occurrence and 0.31 (0.16-0.44) for CP intensity. No evidence emerged for either sex differences in genetic and environmental variance components or interactions of these components with age. Conclusions: Moderate non-additive genetic components were suggested for non-cancer CP occurrence and its intensity. These results encourage further research on the gene-gene interactions underlying CP liability and associated phenotypes, and also strengthen the need for prevention strategies to avoid CP occurrence or to decrease pain intensity.

Development and Validation of the Italian "Brief Five-Item Chronic Pain Questionnaire" for Epidemiological Studies.

Background: Chronic pain (CP) prevalence estimates addressing a wide phenotype are still quite fragmented and may vary widely due to the lack of standardized tools of investigation. There is an urgent need to update general population CP estimates. Methods: For this purpose, the Brief Five-item Chronic Pain Questionnaire was developed through experts' consultations for design and content validity assessment; literature analysis of measures used to investigate CP for general population surveys; understandability evaluation through a survey on a convenience sample of affected and non-affected individuals; reliability assessment by means of two double-wave online surveys carried out by the Italian Twin Registry; criterion and construct validity assessment through the third wave of the 2019 European Health Interview Survey (Ehis). Results: Key dimensions were defined to describe CP main aspects from a public health perspective. Literature analysis showed that validated questionnaires were rarely used to address important public health CP aspects. Understandability of the measure was good. Test-retest analyses showed adequate reliability of the measure: k values were at least "moderate" with highest values regarding CP "occurrence" and "intensity". Correlations of CP with well-known comorbidities (cancer, depression), and specific traits (age, education) as well as of CP and its intensity with "physical pain occurrence and intensity" detected in the Ehis 2019, confirmed, respectively, a good construct and criterion validity. Construct validity was also evaluated through the correlation between "perceived treatment effectiveness" and "interference of pain in daily life activities" as recorded in the Ehis 2019. Conclusion: The designed questionnaire is a brief self-administered measure, particularly suitable to detect persistent states of pain and related intensity in large-scale general population surveys by means of a first filtering item followed by four further items. It is, in fact, designed to detect CP possible underlying causes/triggers, drugs/treatments taking and frequency, and self-perceived effectiveness among CP sufferers. Further validation of the measure in different social and cultural contexts is desirable.

Common-sense model of self-regulation to cluster fibromyalgia patients: results from a cross-sectional study in Italy.

OBJECTIVES: Fibromyalgia is a severe and disabling chronic pain syndrome affecting millions of people worldwide. Various patients' subgroups were identified using different atheoretical measures, hardly effective to tailor treatments. Previous literature findings showed the relevance of fibromyalgia patients' illness perceptions in adjusting to the disease. The present study aims to identify clusters of fibromyalgia patients based on their illness perceptions and investigate whether they can differ across pain, mood, physical functioning, catastrophising, and pain acceptance measures. METHODS: Fifty-three newly referred fibromyalgia patients completed clinical and psychological questionnaires. Patients' subgroups were created by applying hierarchical cluster analysis to their answers to Illness Perception Questionnaire-Revised subscales. Potential differences across subgroups in outcome variables were tested. RESULTS: Cluster analysis identified two patient groups. Group A (32 patients) had a higher representation of fibromyalgia as a chronic disease with severe consequences, lower beliefs in personal and treatment control, and a higher fibromyalgia-related emotional distress than group B (21 patients). Clusters did not differ on pain intensity and duration. Group A, compared to group B, showed worse physical functioning and overall impairment due to fibromyalgia, a poorer psychological condition, a higher tendency to catastrophise, and less pain acceptance. CONCLUSIONS: Study findings reveal two fibromyalgia subgroups differing in emotional suffering and impairment despite similar pain intensity and duration. Patients' illness perceptions and attitudes towards pain, like catastrophising and acceptance, might be critical in adjusting to the disease. A detailed assessment of such risk and protective factors is critical to differentiate patients' subgroups with different needs and thus offering tailored treatments.

Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice.

Chronic pain is nowadays used as an umbrella term referring to a wide range of clinical conditions, such as fibromyalgia, migraine, or long-standing pain states without actual known causes. However, labeling a patient's clinical condition with the term "chronic pain", when dealing with pain lasting longer than 3 months, might be misleading. This paper aims at analyzing the possible pitfalls related to the use of the term "chronic pain" in the clinical field. It appears, indeed, that the term "chronic pain" shows a semantic inaccuracy on the basis of emerging scientific evidences on the pathogenesis of different long-standing pain states. The major pitfalls in using this label emerge in clinical settings, especially with patients having a biomedical perspective on pain or from different cultures, or with healthcare providers of other medical specialties or different disciplines. A label solely emphasizing temporal features does not help to discern the multifaceted complexity of long-standing pain states, whose onset, maintenance and exacerbation are influenced by a complex and interdependent set of bio-psycho-social factors. Thus, finding a more meaningful name might be important. We call upon the necessity of bringing awareness and implementing educational activities for healthcare providers, as well as for the public, on the biopsychosocial approach to assess, prevent and care of chronic pain. Further research on the etiopathogenetic processes of chronic pain states is also required, together with examinative diagnostic methods, to individuate the most appropriate label(s) representing the complex long-standing pain states and to avoid adopting the term "chronic pain" inappropriately.

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases.

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease.